Manusia adalah mesin penghancur diri sendiri yang terbaik. Inilah pelajaran dari sejarah manusia yang manusia sendiri tampak keberatan menerimanya.

Namun, kenyataan lebih banyak membuktikan itu. Berbagai peradaban dunia pupus dan lenyap karena ulah manusia. Bahkan, berbagai bencana alam pelenyap peradaban itu dicari sebab atau mendapatrasionalisasi dati kedegilan makhluk berakal yang membanguin peradaban sendiri.

Tampaknya, itulah yang belakangan kita hadapi. Terkuaknya rekaman pembicaraan yang membongkar drama rekayasa hukum untuk memangkas KPK dan menahan dua komisariatnya seperti banyak puncak gunung kekeliruan peradaban manusia Indonesia. Sedikitnya ada tiga alasan.

Pertama, bila rekaman itu sah dan benar, ia tak hanya membuktikan bagaimana selama ini sistem dan dunia hukum di Indonesia berlangsung lewat transaksi politik dan ekonomi. Kenyataan yang tak hanya menghina dan mengkhianati tujuan dan filosofi dasar dibangunnya sistem hukum, tetapi juga publik sebagai subyek dan obyek hukum itu sendiri.

Kedua, kekeliruan mendasar itu selain menjadi refleksi bagi praksis kehidupan di segmen vital lain – ekonomi, politik, sosial, keamanan, dan lainnya – menunjukkan bagaimana realitas hidup ini dibangun melalui rekayasa semiotik yang menyembunyikan fakta sebenarnya di balik aneka lapisan makna berita-berita yang kita konsumsi tiap hari pada berita utama aneka media massa.

Tragisnya, aneka lapisan tanda (semeio) yang tersembunyi itu tidak membawa kita pada makna yang lebih substansial dan kontemplatif, tetapi tidak lebih dari bongkaran kekerasan kekerasan dan kejahatan manusia yang kian mengerikan. Pengungkapan “kebenaran” melalui rekaman itu memberi lentera bagi pemahaman semiotik publik, tentang permainan keangkaraan apalagi yang masih tersembunyi dalam proses kenegaraan lainnya.

Kesadaran ini seharusnya membyka kita pada kekeliruan di tahap ketiga, di mana manusia Indonesia ternyata adalah pihak yang paling bertanggung jawab pada realitas semiotik yang gelap itu. Bila di permukaan (penanda pertama) manusia tampak cukup ideal dengan produk kulturalnya (seperti regulasi, UU, sistem, dan sebagainya), di lapisan makna berikutnya kita mendapati manusia yang sama, yang ternyata menjadi pengkhianat dan perusak utama produk kultural itu.

Tradisi dua milenia

Akan mencemaskan, bahkan mengerikan, bila pola yang sama ternyata tak berhenti di kalangan elite atau pengambil kebijakan (yang dipercaya dan mendapat fasilitas rakyat), tetapi juga berlangsung di berbagai lembaga lain, secara horizontal maupun vertikal. Di tempat yang bisa jadi kita menemukan diri ada di sotu sebagai pelaku. Inikah karakter dasar kita, sebagai manusia dan bangsa Indonesia ?

Kemungkinan jawaban untuk pertanyaan itu tidak dapat berbentuk pilihan ganda karena semua pilihan dapat benar. Jawaban lebih komprehensif berbentuk esaik, yang melukiskan aneka potensi dasar dari kultur masyarakat/manusia kepulauan yang amat fleksibel dan plastis. Ia bisa positif jika tuntutan dan kondisinya kondusif. Bisa pula bias dan deviatif bila ada keadaan negatif mendesak atau memaksa. Inilah kreativitas, yang selalu memiliki dua wajah (ambigu).

Maka, hal lebih krusial ketimbang tiga alasan kekeliruan adab itu adalah sebuah penegasan perlunya sebuah fondasi (sebuah sistem) nilai yang adekuat untuk mengereksi bangunan kehidupan (modern) yang megah. Dalam arti praktis, material, dan institusional. Dan penegasan ini secara wajar menggiring kita pada kebutuhan akan landasan kebudayaan yang harus dikonstruksi lebih dulu – dengan arsitektur yang kuat – sebagai fondasi gedung megah di atasnya. Bila tidak ingin, aneka bangunan hebat itu (misal sistem ekonomi, politik, hukum, dan sebagainya) rapuh dan rentan pada setiap guncangan pada dimensi apa pun.

Manusia komunal

Saya hanya hendak menyebutkan satu saja dari khazanah tradisi luar biasa itu, yaitu kesadaran manusia kepulauan ini, yang berlaku dalam tradisi di etnik atau subetnik mana pun di seluruh Nusantara, tentang keberadaan dirinya tidak sebagai individu bebas – secara idealis dan relistis – sebagaimana dipahami oleh perikehidupan material-pragmatis saat ini.

Namun, keberadaan itu selalu ada dalam ruang tertentu, dalam waktu tertentu, dalam konteks tertenti : konteks yang mengartikulasi kepentingan komunitas, dalam konteks komunalnya. Manusia adalah individu yang komunal. Demikianlah ekspresi dasar semua lapangan kebudayaan kiota : hidup sosial, ekonomi, artistik, hukum, dan seterusnya.

Apa pun yang dilakukan harus dalam referensi kepentingan komunal sehingga tanpa perlu diminta pertanggungjawabannya, seseorang akan menempatkan publik dalam modus dan tiap aksi eksistensialnya. Di sini publik, yang selalu diingkari, kembali mendapatkan jati dirinya. Dan penyimpangan, apa pun bentuk, tujuan atau maqam-nya, akan mendapat sanksi. Bahkan, sebelum publik atau hukum menjatuhkan dakwaannya.

Maka, di mana lagu peluang elite atau pengambil kebijakan menafikan peran kebudayaan dalam perikehidupan kita berbangsa dan bernegara ? Argumentasi dalam berbagai cara dan fakta, dan puluhan kali saya suarakan, di tengah ketidakpedulian yang ajek di kalangan mereka.

Sumber  :

Kekeliruan Adab Kita, Radhar Panca Dahana | Sastrawan
Kompas, 05.11.2009

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“Candva prindeam aripi si zburam pana la cer. Mai taziu aripile m-au dus acolo unde nu voiam sa ajung. Pe varful cel mai inalt de unde tabla de sah a jocului, demult inceput, imi arata ca am pierdut  partida. Inima refuza sa se resemneze si dicteaza mintii sa construiasca strategii imposibile.. “

…

“In rolul principal o regina nebuna, ce sare calul, face ture si se transforma in pion la nevoie. Ar putea continua la nesfarsit in speranta ca isi va recuceri imperiul. Sa capitulezi cu demnitate poate fi cea mai mare victorie asupra propriei persoane. Intelege.  Regina ratacitoare isi pleaca fruntea, isi striveste lacrimile, isi promite sa uite. Imperiul acesta n-a fost niciodata al ei. Isi ridica privirea spre cer, stie ca atat timp cat n-a pierit speranta, va avea puterea sa paseasca departe, din nou, departe! Intr-o buna zi va construi un imperiul doar al ei , invincinbil. Timpul, viata, timpul… si Dumnezeu o asteptau.”

P.S.! recunoasteti fragmentul?

Imi citeste gandurile si-mi tradeaza temerile.Ma inclin in fata poeziei lui Marin Sorescu.

 Eu mut o zi alba,

El muta o zi neagra.

Eu inaintez un vis,

El mi-l ia la razboi.

El imi ataca plamanii,

 Eu ma gandesc un an la spital,

Fac o combinatie stralucita

 Si-i castig o zi neagra.

El muta o nenorocire

 Si ma ameninta cu cancerul

(Care merge deocamdata in forma de cruce)

 Dar eu ii pun in fata o carte

Si-l silesc sa se retraga.

Ii mai castig cateva piese,

 Dar,uite,jumatate din viata mea

E scoasa pe margine.

 - O sa-ti dau sah si-ti pierzi optimismul,

Imi spune El.

- Nu-i nimic, glumesc eu,

Fac rocada sentimentelor.

In spatele meu sotia, copiii,

Soarele, luna si ceilalti chibiti

Tremura pentru orice miscare a mea.

Eu imi aprind o tigara

Si continui partida.

         *Marin Sorescu,Sah – www.romanianvoice.com

Un alt film dragut de la Pixar…

surpresinhaa ! aqui é a sara gatinha atualizando hihih.. pra falar a verdadade eu nunca fui muito fã de blog não, até porque é muito complicadinho mass a stelluxa teve uma idéia bem legal, então tamo ae! :*)

aqui a gente vai falar um pouco de tudo, música, arte, roupas, cotidiano, de gente etc e etc. Hoje eu vou falar do Andy Warhol um dos melhores artistas da Pop Art, ele retratou diversos artistas de Hollywood, e também trabalhou com as garrafas de Coca-cola e com as latas de sopa Campbell. Pra mim os trabalhos dele são os mais legais, eu adoro, principalmente os da Marilyn Monroe =)

Done it.. hauheuha da proxima vez, i promise, eu penso em um post melhorziinho! besistos, fiquem com a marylinzinha :*

This article indicates Thimerosal levels contained in vaccinations can completely eliminate methionine synthase activity.  Blocking or eliminating methionine synthase activity could cause attention deficit disorders and contribute to Autism and elevated homocysteine levels, which could increase cardiac risk.

Fall Defeat Autism Now!^TM 2003 Conference *** Portland, Oregon *** October 3-5, 2003

Effects of Mercury on Methionine Synthase: Implications for Disordered Methylation in Autism

Richard Deth, PhD and Mostafa Waly, PhD
Northeastern University, Boston, MA 02115

Methionine synthase carries out the vitamin B12-dependent methylation of homocysteine, using a methyl group from 5-methyltetrahydrofolate (5-methylTHF). In doing so it provides a crucial link between two important metabolic systems, the single-carbon folate pathway and the methionine cycle (Fig. 1, right). Recently our laboratory discovered that methionine synthase is also required for dopamine-stimulated methylation of membrane phospholipids, a unique signaling activity of the D4 dopamine receptor (1-3). In the latter case, a homocysteine residue in the D4 receptor, generated by donation of a methyl group to the phosphatidylethanolamine (PE), is re-methylated to methionine, with 5-methylTHF again serving as a co-factor (Fig. 1, left). Thus methionine synthase also links dopaminergic neurotransmission to metabolism.

Figure 1. Pathways of single-carbon metabolism. The folate pathway (middle) supplies formate-derived single-carbon groups for purine and thymidine synthesis and methyl groups (as 5-methylTHF) to methionine synthase (Met Syn). The methionine cycle (lower right) provides S-adenosylmethionine (SAM), the methyl donor for many methylation reactions. MET313 in the D4 receptor also serves as a donor of methyl groups for methylation of the phospholipid phosphatidylethanolamine (PE).

Sufficient methylation of homocysteine is essential not only to supplement the diet-derived supply of methionine, but also to maintain a low level of homocysteine and its precursor, S-adenosylmethionine (SAH), which otherwise inhibits methylation reactions by competing with the methyl donor S-adenosylmethionine (SAM). Increased methionine synthase activity can therefore promote methylation by lowering SAH, while impaired activity will impede methylation.  In addition, THF released by methionine synthase is needed for other folate-dependent reactions, avoiding a “methyl-folate trap”.

D4 receptor-mediated phospholipid methylation (PLM) can be very robust, up to 50 methylations/receptor/sec, increasing the spacing between phospholipid headgroups and altering the fluid properties of the membrane in the region surrounding the receptor. The activity of membrane proteins located near the D4 receptor can be modulated by PLM and this “solid-state signaling” mechanism has been implicated in the molecular mechanism of attention (4). Proline-rich segments present in the cytoplasmic portion of the receptor in all species allow it to serve as a docking site for signaling proteins that become targets for PLM-based modulation. In humans and other primates, the D4 receptor possesses anywhere from 2 to 11 additional proline-rich repeat segments (Fig. 2), and a higher number of repeats (i.e. seven) brings an increased risk of attention-deficit hyperactivity disorder (ADHD) (5). Thus methionine synthase activity is important for normal attention while a decrease in its activity may contribute to ADHD.

Figure 2. Structural features of the D4 dopamine receptor. Methionine 313 serves as donor of methyl groups to the headgroups of surrounding phospholipids. Proline-rich segments allow other proteins to bind to the D4 receptor.

Methionine Synthase is Regulated by IGF-1 and Dopamine

Recently our laboratory has showed that the enzymatic activity of methionine synthase in human neuroblastoma cells is increased by stimulation of either D4 dopamine receptors or insulin-like growth factor-1 (IGF-1) receptors (6). In intact cells, this stimulation is evident as an increase in the rate of folate-dependent phospholipid methylation (Fig. 3), while pretreatment of cells with IGF-1 or dopamine or their combination increased the enzyme activity of methionine synthase by more than five-fold (Table 1).

Figure 3. Dose-dependent stimulation of folate-dependent phospholipid methylation (PLM) by IGF-I in SY5Y neuroblastoma cells.

Further investigation revealed that stimulation of methionine synthase by dopamine and IGF-1 involves activation of the PI3-kinase signaling pathway. Via different mechanisms, D4 and IGF-1 receptor activation leads to increased phosphorylation of plasma membrane inositol phospholipids by PI3-kinase. Numerous studies have shown that activation of this pathway by IGF-1 promotes cell survival while activation by other growth factors (e.g. nerve growth factor) leads to cellular differentiation. Moreover, interference with the methionine cycle blocks the ability of nerve growth factor to induce differentiation (7). Inhibition of PI3-kinase not only blocked stimulation of methionine synthase by dopamine and IGF-1, but also reduced enzyme activity to zero (Table 1), indicating an absolute dependence on PI3-kinase in the human neuroblastoma cells we used. This is the first report that extracellular signaling molecules can regulate methionine synthase.

By increasing methionine synthase activity, IGF and dopamine will decrease the levels of both homocysteine and SAH, increasing the SAM to SAH ratio and thereby promoting methylation reactions. Methylation of DNA leads to the formation of nucleosomes (stable complexes of DNA and histones), causing gene silencing. We measured global DNA methylation after a 6-hour treatment with IGF-1 or dopamine and found increases of 101% and 71% respectively, which were blocked by an inhibitor of PI3-kinase (6). Furthermore, PI3-kinase inhibition decreased methylation of the cyclin D2 gene, and increased its transcription. Together these observations indicate that PI3-kinase-dependent activation of methionine synthase provides a mechanism by which IGF-1 and dopamine can regulate gene expression via changes in DNA methylation.

Neurodevelopmental Toxins Inhibit Methionine Synthase

Environmental exposure to heavy metals, such as lead and mercury, causes neurotoxicity and leads to developmental disorders. It has been proposed that the recent dramatic rise in the incidence of autism is linked to the increased number of required vaccinations containing the ethylmercury derivative thimerosal (8,9). Since developmental disorders such as Rett syndrome and fragile-X syndrome include a crucial role for DNA methylation, we investigated the effects of various metal ions on methionine synthase activity and folate-dependent PLM.

As shown in Table 1, treatment of neuroblastoma cells with mercury (1 mM) or thimerosal (10 nM) for 60 min caused a complete loss of measurable methionine synthase activity, while lead significantly reduced enzyme activity. Ethanol, a well-recognized neurodevelopmental toxin, also eliminated activity at a concentration of 0.1%. Folate-dependent PLM studies (Fig. 4) showed that mercury and lead produced dose-dependent inhibition with a threshold near 1 nM, while thimerosal was at least 10-fold more potent. It is notable that a single dose of thimerosal-containing vaccine produces blood levels between 10 and 100 nM (10). These results clearly demonstrate the ability of neurodevelopmental toxins and thimerosal to inhibit PI3-kinase-dependent methionine synthase activity. Additional studies indicated that heavy metal-induced inhibition is likely caused by competition with Cu²⁺, which is required for PI3-kinase activity (6). In contrast, ethanol acts by interfering with IGF-1 receptor activation.  EMPHASIS ADDED

Table 1 Effect of IGF-1, dopamine and neurodevelopmental toxins on methionine synthase activity. IGF-1 and dopamine increase activity by 2.3- and 2.8-fold respectively. The PI3-kinase inhibitor wortmannin reduces activity to undetectable levels and blocks stimulation.The neurodevelopmental toxins ethanol, mercury, lead and thimerosal either inhibit or eliminate methionine synthase activity.

Figure 4. Inhibition of folate-dependent PLM by mercury, lead and thimerosal. Mercury and lead exhibit a threshold near 1 nM for inhibition of IGF-1-stimulated PLM (Left panel). Thimerosal inhibits both basal PLM and stimulation by either IGF-1 or dopamine at concentrations of 0.1 nM and higher (Right panel).

Implications for Autism

It has been proposed that the recent dramatic increase in the incidence of autism is due to neurodevelopmental effects of thimerosal, associated with an increase in the number of required vaccines containing this preservative (8,9). However, this proposal has met with considerable skepticism, since there was no evidence that thimerosal could produce adverse effects on a relevant biochemical process at the concentrations produced by vaccination. A single vaccination produces blood levels between 10 and 100 nM (10). Our findings clearly demonstrate that thimerosal inhibits PI3-kinase-dependent methionine synthase at concentrations well below these levels, raising the possibility that this inhibition might contribute to the pathology of autism.

Several important questions arise: 1. How might lower methionine synthase activity account for the symptoms of autism? 2. What are the risk factor(s) for developing autism?

As noted above, methionine synthase has two substrates: the homocysteine state of the D4 dopamine receptor and homocysteine itself. Reduced activity will therefore decrease D4 receptor-mediated PLM and increase homocysteine levels. Since D4 receptor-mediated PLM appears to be important for the molecular mechanism of attention (4), its impairment could lead to a reduced capacity for attention, which is a primary symptom of autism. Indeed, autism shares several features with ADHD, including a 3-4-fold higher prevalence in males vs. females and both conditions have shown a markedly higher incidence over the past several decades. Reduced activity of methionine synthase, caused by exposure to heavy metals and/or thimerosal, could therefore impair the molecular mechanism of attention, leading to symptoms of autism. ADHD may represent a milder form of autism, associated with moderate inhibition of D4 receptor-mediated PLM.

Since SAH hydrolase (Ado HCYase in Fig. 1) is reversible, a failure of methionine synthase to efficiently convert homocysteine to methionine will lead to increased formation of SAH, to an extent dependent upon the prevailing concentration of adenosine. SAH inhibits methylation reactions, and decreased methionine synthase activity could therefore reduce DNA methylation, resulting in altered patterns of gene expression and impaired development. More specifically, heavy metals and thimerosal may interfere with the ability of growth factors like IGF-1 to promote development by impairing their control over methionine synthase.

The risk of developing autism in response to heavy metal or thimerosal exposure may depend upon genetically-transmitted risk factors that interact with methylation events. For example, previous studies showed that adenosine deaminase (ADA) activity is reduced in autistic individuals (11), associated with increased prevalence of a polymorphism in the ADA gene that reduces enzyme activity (12). As illustrated in Fig. 1, reduced ADA activity will cause elevated adenosine levels that will synergize with impaired methionine synthase activity to produce higher levels of SAH, yielding greater inhibition of methylation reactions. Increased synthesis of adenosine due to elevated 5’-nucleotidase activity has also been reported in autism (13). Mutations in the adenosylsuccinate lyase (ASL) gene are a rare cause of autism (14). These mutations divert single-carbon groups toward de novo purine synthesis and limit the availability of 5-methylTHF. Moreover, increased purine synthesis is common in autism (15). Lower availability of 5-methylTHF will synergize with the inhibitory effects of metals and thimerosal. These examples serve to illustrate how genetic and metabolic abnormalities can predispose to autism. Any impairment in the ability to excrete or detoxify heavy metals will also impose a further increased risk (16).

Summary

Our studies provide new insights into the control of methylation reactions by dopamine and by growth factors that increase PI3-kinase. By increasing methionine synthase activity and accelerating the conversion of homocysteine to methionine, they can lower SAH levels and promote methylation reactions. Neurodevelopmental toxins and thimerosal interfere with PI3-kinase-dependent methionine synthase, resulting in impaired methylation, including DNA methylation that is essential for normal development. D4 receptor-dependent PLM is an essential component of the molecular mechanism of attention, and reduced methionine synthase activity will therefore lead to impairments in attention and in attention-related learning. ADHD may reflect a milder degree of impairment in these same mechanisms. Since thimerosal has largely, but not completely, been eliminated from vaccines in the U.S., it will be of particular interest to observe whether the incidence of autism decreases during the next 3-5 years. Finally, we hope that these findings may point the way toward the discovery of new therapeutic approaches for the treatment of autism as well as new diagnostic tests that could identify individuals at high risk of developing autism in response to thimerosal or heavy metal exposure.

References

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2. Zhao, R., Chen, Y., Tan, W., Waly, M., Sharma, A., Stover, P., Rosowsky, A., Malewicz, B., & Deth, R.C. (2001) J. Neurochem. 78, 788-96.
3. Sharma, A., Waly, M., & Deth, R.C. (2001) Eur. J. Pharmacol. 427, 83-90.
4. LaHoste, G.J., Swanson, J.M., Wigal, S.B., Glabe, C., Wigal, T., King, N., & Kennedy, J.L. (1996) Mol. Psychiatry 1, 121-4.
5. Deth, R.C. (2003) in Molecular Origins of Human Attention, (Kluwer Academic Publishers, Boston).
6. Waly, M., Olteanu, H., Banerjee, R., Choi, S.-W., Mason, J., Parker, B., Sukumar, S., Shim, S., Sharma, A., Benzecry, J., Power-Charnitsky, V.-A., & Deth, R.C. (Submitted)  Molec. Psychiatry.
7. Cimato, T.R., Ettinger, M.J., Zhou, X.& Aletta, J.M. (1997) J. Cell Biol. 138,1089-103.
8. Bernard, S., Enayati, A., Roger, H., Binstock, T., & Redwood, L. (2002) Mol. Psychiatry 7, S42-3.
9. Geier, M.R. & Geier, D.A. (2003) J. Am. Phys. Surg. 8, 6-11.
10. Stajich, G.V., Lopez, G.P., Harry, S.W., & Sexson, W.R. (2000) J. Pediatr. 136, 679-81.
11. Stubbs, G., Litt, M., Lis, E., Jackson, R., Voth, W., Lindberg, A., Litt, R. (1982) J. Am. Acad. Child Psychiatry 21, 71-4.
12. Persico, A.M., Militerni, R., Bravaccio, C., Schneider, C., Melmed, R., Trillo, S., Montecchi, F., Palermo, M.T., Pascucci, T., Puglisi-Allegra, S. et al. (2002) Am. J. Med. Genet. 96, 784-90.
13. Page, T., Yu, A., Fontanesi, J., Nyhan, W.L. (1997) Proc. Natl. Acad. Sci. U S A 94, 11601-6.
14. Stone, R.L., Aimi, J., Barshop, B.A., Jaeken, J., Van den Berghe, G., Zalkin, H., & Dixon, J.E. (1992) Nat. Genet. 1, 59-63.
15. Page, T., & Coleman, M. (1998) Adv. Exp. Med. Biol. 431, 793-6.
16. Blaxill, M. F. & Haley, B.E. (2003) Int. J. Toxicol. 22,

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